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POS0049 CLINICAL AND RADIOGRAPHIC RESULTS OF TAPERING AND WITHDRAWING CSDMARDS VERSUS STABLE TREATMENT IN RHEUMATOID ARTHRITIS REMISSION: 3-YEAR RESULTS FROM A RANDOMIZED CONTROLLED TRIAL

2023; BMJ; Linguagem: Inglês

10.1136/annrheumdis-2023-eular.415

1468-2060

Kaja E Kjørholt, Nina Paulshus Sundlisæter, Anna‐Birgitte Aga, J. Sexton, Inge Christoffer Olsen, Hallvard Fremstad, C. Spada, T. M. Madland, Christian Høili, Gunnstein Bakland, Åse Stavland Lexberg, Inger Johanne Widding Hansen, Inger Marie Jensen Hansen, Hilde Haukeland, M. K. A. Ljosa, Ellen Moholt, Till Uhlig, Tore K Kvien, Daniel H. Solomon, Désirée van der Heijde, Espen A. Haavardsholm, Siri Lillegraven,

Rheumatoid Arthritis Research and Therapies

Background Tapering of disease modifying antirheumatic drugs (DMARDs) to achieve drug-free remission is a goal for the growing group of rheumatoid arthritis (RA) patients in remission. However, the long-term effects of tapering or withdrawal of DMARDs remain unclear. Objectives To compare the 3-year clinical and radiographic outcomes of three conventional synthetic DMARD (csDMARD) treatment strategies (continued stable treatment, half-dose treatment and tapering to withdrawal) among patients in sustained RA remission. Methods ARCTIC REWIND was a randomized, multicenter, open-label, clinical trial enrolling 160 RA patients in sustained remission for ≥1 year on stable csDMARD therapy from 10 different Norwegian rheumatology departments.(1) At baseline, patients were randomized 2:1:1 to stable csDMARDs, half-dose csDMARDs, or half-dose csDMARDs for one year, followed by withdrawal of all csDMARDs ("tapering to withdrawal"). The primary endpoint was absence of disease activity flare over the 3-year study period. A flare was defined as a combination of disease activity score (DAS)>1.6, an increase in DAS ≥0.6 units since the previous visit and ≥2 swollen joints, or if the physician and patient agreed that a clinically significant flare had occurred. Full-dose csDMARD treatment was reinstated upon flare. Secondary endpoints included remission (DAS, ACR/EULAR Boolean) at 1, 2 and 3 years, and 3-year change in radiographic joint damage evaluated by van der Heijde-Sharp score (vdHSS). Data were analyzed using Kaplan-Meier, Mann-Whitney test, Cox and mixed effect logistic regression, with stratification or adjustment for study center. Results Of 156 patients who received the allocated treatment strategy, 139 patients completed 3-years follow-up without major protocol violation. Mean baseline methotrexate dose/week was 19.0 mg in the stable group, 19.4 mg in half-dose, and 19.5 mg in the withdrawal group, and mean DAS at baseline was 0.8 in all groups. During the 3-year study period, 80.1% remained flare-free in the stable csDMARD group, 59.5% in the half-dose and 40.8% in the withdrawal group ( Figure 1 ), with corresponding adjusted hazard ratio (aHR) for flare of 2.7 (95% CI: 1.3 to 5.5) in the half-dose group and 4.1 (2.1 to 8.0) in the withdrawal group, compared to stable csDMARD. The aHR was 1.5 (0.8 to 3.0) in the withdrawal group compared to the half-dose group. For all groups, a majority were in remission at 1, 2 and 3 years (Table 1 ), with the only significant group difference for ACR/EULAR Boolean remission at 3 years, with risk difference for withdrawal vs stable dose -25% (-45 to -6). Mean/median change in vdHSS after 3 years were 0.3/0.0 in the stable group, 1.0/0.5 in the half-dose group, and 0.7/0.0 in the tapering to withdrawal group, with significant difference between the stable and half-dose group, p<0.01. Sensitivity analyses in the full analysis population gave similar results. Conclusion These 3-year data show that 41% of patients in the tapering to withdrawal arm achieved long-term drug-free remission, indicating that this is a realistic option for some RA patients in sustained remission. The two tapering strategies were associated with an increased risk of flares compared to full-dose csDMARD, and the half-dose group had more radiographic change. However, there were no differences in DAS-remission at the end of the study period. Further research identifying prognostic factors for successful tapering is needed. Reference [1]Lillegraven S et al. JAMA 2021 Acknowledgements: NIL. Disclosure of Interests Kaja Kjørholt: None declared, Nina Paulshus Sundlisæter: None declared, Anna-Birgitte Aga Speakers bureau: AbbVie, Eli Lilly, Novartis, Pfizer, Consultant of: AbbVie, Eli Lilly, Novartis, Pfizer, Joseph Sexton: None declared, Inge Olsen: None declared, Hallvard Fremstad: None declared, Cristina Spada Consultant of: Advisory board UCB November 2022, Tor Magne Madland Speakers bureau: Cellgene (2017), Novartis (2018), Boehringer (2022), Christian A. Høili: None declared, Gunnstein Bakland Consultant of: Consultant fee from UCB, Åse Lexberg: None declared, Inger Johanne Widding Hansen: None declared, Inger M. Hansen: None declared, Hilde Haukeland Consultant of: Advisory board for UCB Pharma 2x in 2022, NovartisNorge 2017 and 2018, Abbot 2012, Maud-Kristine A Ljosa Consultant of: Advisory Board for Abbvie i 2022, Ellen Moholt: None declared, Till Uhlig Speakers bureau: Lilly, Galapagos, Pfizer, UCB, Consultant of: Lilly, Galapagos, Pfizer, UCB, Tore K. Kvien Speakers bureau: Grünenthal, Sandoz, UCB, Consultant of: AbbVie, Amgen, Celltrion, Gilead, Novartis, Pfizer, Sandoz, UCB, Grant/research support from: AbbVie, Amgen, BMS, Galapagos, Novartis, Pfizer, UCB, Daniel Solomon Grant/research support from: Abbvie, Amgen, CorEvitas, Moderna, and Janssen, Désirée van der Heijde Consultant of: AbbVie, Bayer, BMS, Cyxone, Eisai, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Lilly, Novartis, Pfizer, UCB Pharma Director of Imaging Rheumatology bv, Espen A Haavardsholm Speakers bureau: Pfizer, UCB, Consultant of: AbbVie, Boehringer Ingelheim, Eli Lilly, Gilead, Siri Lillegraven Grant/research support from: Boehringer Ingelheim.